15 June 2018

Why is there so little love for LARCs?

Clinical Women

There is a law of innovation that goes something like this: effectiveness x acceptability = actual value of a solution. In other words, even the most perfect remedy will fail if, for whatever reason, people don’t want to use it. 

The medical literature crowns long-acting reversible contraception (LARCs) as the most effective method for preventing pregnancy, but the rate of uptake in Australia is snail-like. Only around 6% of Australian women use an IUD and 5% use an implant, while one-third rely on oral contraceptives. 

From a public-health perspective, the current contraception used by Australian women is inadequate. Around half of Australian women experience an unintended pregnancy in their lifetime, despite the majority of women using some form of contraception when they are not trying to get pregnant. 

LARCs are more effective than the pill; less than one in every 100 LARC users get pregnant in a year, compared with six to nine women per 100 using the pill. 

These “set and forget” devices commonly release progestogen around the clock for three to five years, freeing women from daily medication regimens. And LARCs are usually cheaper than the pill in the long run, with an up-front cost of around $40 to $200 compared with the pill’s yearly cost of about $35 to $290. 

If every Australian woman using contraception switched to a LARC, the number of unplanned pregnancies could be reduced substantially. This would reduce the annual abortion rate, which currently sits at around 13.5 per 1,000 women. It could also lower the risk of gestational diabetes, preeclampsia, caesarean section, and lift the financial burden placed on pregnant teenagers.

LARCs have been endorsed by the World Health Organisation and the United Nations, and are used by over a 160 million women worldwide, with a low rate of serious adverse effects. 

ADVERSE MEDIA EVENTS

LARCs seem like the ideal solution to unplanned pregnancy, but the mainstream media in Australia have a darker story to tell. The ABC’s 7.30 Report went to air late last year with a series of traumatic stories involving LARCs. 

One woman said she bled for seven months after being having an implant inserted into her arm. Another said the Mirena caused severe cramping, bleeding, sweats, headaches, nausea and anxiety, and said she would have to wait a year to have it removed in a public hospital. 

These weren’t isolated incidents; more horror stories bubbled to the surface over the past few months. An Australian woman spoke publicly about her experience of almost bleeding to death two days after a Mirena was inserted. (Her GP failed to correctly identify her as having an retroverted cervix, meaning that her cervix was tilted. Women with a retroverted cervix can use a Mirena, but they are at risk of perforation if the device is put in the wrong place.)

In another personal account, published by News Corp Australia in April, freelance writer Koraly Dimitriadis described her experience of pelvic inflammatory disease, which is a known, but very uncommon, adverse side effect of having a Mirena inserted. 

This story was the straw that broke the camel’s back for The Royal Australian and New Zealand College of Obstetricians and Gynaecologists, which issued a statement condemning the media’s “irresponsible reporting” of negative experiences with IUDs. 

“It is important to talk about adverse effects but in context, so actually looking at the number of people who use them and how common adverse events are – and, in general, they are not common,” Dr Charlotte Elder, an obstetrician gynaecologist and a spokesperson for RANZCOG, told The Medical Republic. 

The media has a deep-seated bias towards negative news stories (‘If it bleeds, it leads’). “There are lots of women for whom an IUD has turned out to be fantastic but you don’t see those stories,” Professor Meredith Temple-Smith, a GP academic at The University of Melbourne, said.

The negative news coverage seems to be driven by a fear that pharmaceutical companies are downplaying the side effects of LARCs, and influencing doctors by sponsoring education events. However, a closer inspection of the figures reveals that manufacturers are actually doing the opposite –  Merck and Bayer are both overestimating the risks associated with LARCs.

Around one million women in Australia have used Implanon in the past decade, with around 1,000 side effects reported to the TGA in total. This is a rate of about 0.1%, which is a hundred times lower than the 10% estimate published on Merck’s website. 

Out of about one million women with a Mirena, over 850 reported adverse effects to the TGA. This is a rate of about 0.085%, which is much less than the 1 in 10 rate reported by Bayer. 

The real-life rate of unintended pregnancies with Mirena was 0.007%, and 0.05% with Implanon – far less than the 1% failure rate advertised by both Bayer and Merck. 

There is no evidence to suggest that the rates of adverse effects of the Mirena and Implanon are higher than expected, a TGA spokesperson tells The Medical Republic. 

It may be that side effects of LARCs are being under-reported by doctors, as some women claim. But the TGA also accepts adverse event reports directly from consumers, so a spike in serious side effects is unlikely to go unnoticed by the regulator. 

“Lousy stuff will out eventually,” Dr Terri Foran, a sexual health physician at UNSW, said. “When terrible things start to happen in large numbers I think that clinicians do, in fact, mobilise.” 

Medical device regulation is all about balancing risk and benefits – and, as recent events show, that balance can tip quickly. Unacceptable rates of adverse events led to the TGA outlawing of the Essure device, and the vaginal mesh implant for prolapse, last year. 

Mounting litigation can also force manufacturers to stop making a product.

 In the US, thousands of women are already pursuing legal action against Bayer, claiming that the Mirena caused perforation, migration, pelvic inflammatory disease, ectopic pregnancy, and painful surgeries. 

Dr Foran said it would be a shame to lose such a beneficial device due to a small number of expected adverse events. The Mirena was not only useful for contraception, it was used for management of menopause, heavy bleeding, and endometriosis, she said. 

The Mirena was also credited with the three-fold reduction in hysterectomies in one generation. 

WHAT’S UP DOWN UNDER?

Australia is well behind the rest of the world in terms of its uptake of IUDs. Around 14% of women with partners use IUDs worldwide, while only around 6% of Australian women choose this option. (Implants are less popular worldwide, with an uptake of only 0.7%.)

Some national governments have decided to push LARCs as a way of reducing the rates of unintended pregnancy and termination. In the UK, for instance, government initiatives have increased the rate of IUD use to 10%, which has probably helped lower the rate of unplanned pregnancy down to around 30%.

“In Australia, I don’t think that we’ve put the same amount of effort and energy into educating both women and doctors around the advantages of LARCs,” Dr Foran said.

“Reproductive health is seen as somewhat of a secondary consideration in this country.  The main opinion leaders in contraception in Australia are the family planning organisations, which are very small and poorly funded.”

The country with the greatest uptake of LARCs is China, with an IUD rate of 37.7%. During the era of the one-child policy, IUDs were the contraception of choice for the medical service in China. “And that exists until the present day,” Dr Foran said. 

The shift towards LARCs is so strong that Chinese women now tend to view oral contraceptives with suspicion, which is analogous to the negative attitudes towards LARCs in Australia. 

The Mirena was developed in Finland, which may explain the rapid uptake in across Scandinavia, Dr Foran said. Norway, for instance, has IUD use rates of 20%. 

Northern Europe also wasn’t touched by the IUD scandal of the 1970s, which hit Australia, the US and New Zealand. 

Nearly 50 years ago, a stingray-shaped IUD called Dalkon Shield resulted in one of the largest personal injury law suits in American history when it caused 18 deaths, 242 septic abortions, pelvic infections, ectopic pregnancies, hysterectomies, infertility from scarring. 

The manufacturer, A. H. Robins Company, tried to cover up the fact that they were aware of the dangers of the device. By the 1980s, the company was facing lawsuits totalling $12 billion from around 300,000 US women and 6,000 Australian women. 

Even though this story has largely been forgotten, the feeling of distrust lingers (only 5% of women use IUDs in the US). “Particularly older doctors, and even the older parents, they remember,” Professor Temple-Smith said. 

Once the seeds of doubt are sewn, it’s very difficult to undo that damage. 

GENUINE CONCERNS?

The least medically important side effects of LARCs, such as annoying changes to menstrual bleeding, are enough to put many women off.

Changes to bleeding patterns are the most common side effect of progestogen-only contraceptives, including the Implanon and Mirena, and are the main reason women discontinue these methods. 

In the first three to six months of using a Mirena, bleeding can be extremely unpredictable, but the total volume of bleeding usually decreases. After two years of use, about 50% of women report amenorrhoea, about 10% have spotting, and 25% have infrequent periods. 

Around 20% of women using the Implanon develop amenorrhoea, while 20% have frequent or prolonged bleeding. Some women bleed continuously. This doesn’t settle over time; the bleeding pattern of the first three months is broadly predictive of the future.

Whether these side effects are acceptable depends on the woman’s individual preferences. 

While some women absolutely love not having to deal with periods ever again, some women dislike having no bleeding.

 “So, it’s very individual what people find troublesome,” Associate Professor Deborah Bateson, the medical director at Family Planning NSW, said. 

“The key message to women is that they can seek help and advice if they are experiencing side effects. And that may also mean, obviously, taking out that LARC. It’s about listening to the woman’s experience and ensuring that we follow her wishes.”

An “internment trickle” of blood could also be intolerable for some women, particularly those who avoided sex during menstruation, Professor Juliet Richters, an epidemiologist at the Kirby Institute for Infection and Immunity in Society, said. 

“This is something they don’t talk to their doctor about. They just go back to their doctor and say they want to have the IUD out.” Many of the issues that women have with LARCs are non-medical, says Professor Richters. Some women feel squeamish about having a device inserted into their body. 

Others fear being robbed of bodily autonomy because they have to rely on a doctor to remove the device.

“The way women think about their bodies are not the same way that doctors do,”  Professor Richters said.

The combined oral contraceptive (COC) pill also causes irregular bleeding in up to 20% of users. This usually settles over time, and women are recommended to keep taking the pill for at least three months before switching medications. 

The COC pill also increases the risk of blood clots two to three-fold, raising the rate of VTE (deep vein thrombosis and pulmonary embolism) to five to 12 per 10,000 women per year. 

The pill, the Mirena and the Implanon are all associated with hormonally related side effects, including mood changes.

The COC pill has been shown to increase the risk of depression, with around one additional prescription for antidepressants for every 300 women on the pill, and one women receiving a hospital diagnosis for depression for every 5,000 women on the pill. 

The pill tends to improve acne, whereas the Mirena and Implanon can aggravate the condition. Women using the Implanon and Mirena have reported breast tenderness, headaches and reduced libido. 

The Mirena is also associated with weight gain, but the Implanon and the pill aren’t. 

For a more detailed discussion of side effects, Professor Bateson recommends The Faculty of Sexual and Reproductive Healthcare’s online resources (bit.ly/2kpn6Rq).

BARRIERS TO ACCESS

For many Australian women choosing the pill, it’s not that they have specific objections to LARCs, it’s just that they have no idea that LARCs are an effective alternative contraception. 

“Ideally, people would know enough from sex-ed at school that there is a range of methods, but that doesn’t always happen,” Professor Richters said. “Obviously, they can get leaflets and look things up online, but then people tend not to look up something they haven’t heard of.”

Well-educated, high-earning women aged over 30 have the highest uptake of IUDs in Australia. These women know their bodies well, are more empowered than teenagers, and are more likely to have seen a specialist about reproductive health in their lifetime. 

GPs work under time constraints and are unlikely to take women through all the options for contraception unless the patient expresses a particular interest. There is also a long-standing misconception among doctors that IUDs are not an appropriate first-line method of contraception for nulliparous women or teenagers.

On top of this, there is little financial incentive for Australian GPs to upskill in LARC insertions. The training is expensive and time-consuming, and with so little interest in LARCs, it is not always possible to keep these skills polished. 

Patients often have to book a specialist appointment to have a LARC inserted, which increases the wait time, travel time and expense. 

However, studies show that when all these barriers are removed, a hidden market for LARCs bursts into existence. The CHOICE project, involving around 5,000 US women, showed that two-thirds of patients chose LARCs when GPs presented this option first and LARCs were inserted at no charge. 

In this study, IUD and implants had strikingly higher rates of satisfaction than the pill, depot injections, patches and the vaginal ring. LARCs had an 86% one-year continuation rate compared with 55% for the oral contraceptive pill.

This US study inspired an Australian spin-off called the ACCORd study. The results of this four-year trial are now awaiting publication, but project manager and nurse Dr Cathy Watson (PhD) said we’d have to wait a few months to find out whether LARC uptake had increased.

Intriguingly, almost all female gynaecologists use a LARC. “And I suppose that’s where we put our money where our mouths are,” Dr Elder said. “We use what we are recommending for our patients.”

Declarations of conflicts of interest:

Dr Terri Foran has provided expert opinion and developed and delivered educational material for Bayer, Merck Sharp and Dohme, Teva and Pfizer who market contraceptive products in Australia. Dr Foran has also received support for conference attendance from Bayer. She also works as a sub investigator for the research unit at the Royal Hospital for Women in Sydney which has in the past investigated contraceptive products. Dr Foran holds no stock nor has any commercial interest in any contraceptive products. 

Dr Charlotte Elder is a prescriber and inserter of LARCs. 

Professor Juliet Richters has not had any funding or other support from any pharmaceutical company. She has not had close contact with anyone who has had catastrophic experiences with LARCs or any other contraceptive method.

Professor Deborah Bateson has attended advisory forums and presented at educational events for Bayer Healthcare and MSD as part of her role as medical director of Family Planning NSW, but has never been personally remunerated for these services. She has been supported to attend conferences by Bayer Healthcare.

Professor Meredith Temple-Smith has no declaration of conflicts of interest. 

COVID-19 live update